Researchers from NIMH's Neuropsychiatry Branch, together with colleagues at Columbia University and the Kaiser Permanente Division of Research, continued work on the observational Prenatal Determinants of Schizophrenia (PDS) study. The study group comprised 19,044 infants born between 1959 and 1967 in the prepaid Kaiser-Oakland Healthcare System. The pregnancies were carefully monitored with standardized instruments, and sera from each trimester were preserved, as well as cord blood. The unified records were computerized and the subjects continuously followed until they dropped out of the healthcare system. PDS tracked 12,576 of these subjects into adulthood. To date, 71 of these individuals have been identified as having a schizophrenia spectrum disorder. When possible, diagnosis was made through interviews with the subject. The investigators compared prenatal exposures for the individuals with schizophrenia spectrum disorder against appropriate controls from the same cohort. A series of articles published in 2000 set out two important findings: the mothers of the individuals who would eventually develop a schizophrenia spectrum disorder had: 1) an elevated prepregnancy body mass index (BMI), and 2) an excess of second trimester respiratory infections. BMI is a ratio of weight to height [(weight in pounds/height in inches)2 x 704.5]. More recently, the researchers explored the links between advancing paternal age and the risk of schizophrenia in 71 subjects with schizophrenia or schizophrenia spectrum disorders. Virtually all members of the PDS birth cohort had prospective information about paternal age at the time of the offspring's birth. In separate analyses, paternal age was modeled as a continuous variable and as a categorical variable, and its relation with the risk of adult schizophrenia and other schizophrenia spectrum disorders and with the risk of schizophrenia separately were examined. There was a marginally significant, monotonic association between advancing paternal age and risk of adult schizophrenia and schizophrenia spectrum disorders. The association held after the analysis controlled for the effects of maternal age and other potential confounders. Similar results were observed when only subjects with schizophrenia were included in the analysis. These results suggest that advanced paternal age at the time of birth of the offspring may be a risk factor for adult schizophrenia, and add significantly to our understanding of possible etiologies in the development of this disorder.